Anal cancer is predominantly a disease of women, among whom the incidence is rising at an annual rate of nearly 2%. Recent studies have shown that the incidence of anal cancer has increased among men with AIDS, and that HIV+ men have a very high prevalence of anal human papillomavirus (HPV) infection and potentially precancerous anal abnormalities. At this time, however, nothing is known about the natural history of anal HPV infection, anal cancer and its precursor lesions in women, and it is not known if HIV+ women are at higher risk than HIV - women. Recently, we performed a pilot study of HIV+ and HIV - women to determine prevalence of anal HPV infection and anal cytologic abnormalities in these groups. The results of this study were very provocative, in that the prevalence of anal HPV infection was double that of the cervix, and anal cytologic changes were at least as common as those of the cervix. Most of the anal changes were detected in the HIV+ women, who were found to have a prevalence of 77% of anal HPV infection using polymerase chain reaction. To begin to address these issues, we are proposing a 4 year prospective study to elucidate the natural history of, and risk factors for anal HPV infection and potentially precancerous anal disease in HIV+ and HIV - women. We will study 250 HIV+ and 250 HIV - women who are already participating in an ongoing natural history study of HIV disease (the Bay Area Research Consortium on Women and AIDS, or BARCWA). Women will be assessed every 6 months with a questionnaire detailing behavioral and other risk factors for anal disease, anal HPV testing, anal cytology and anoscopy with biopsy of visible disease. At each visit, as part of the BARCWA study, each subject will also undergo cervical cytology and cervical HPV testing, as well as an extensive battery of other tests and a detailed questionnaire that complements that of the proposed study of anal disease. Women who develop high grade anal intraepithelial neoplasia (AIN) will be removed from follow-up and referred for treatment; women with low grade AIN will be followed every 3 months. Like cervical cancer, anal cancer may be preventable with appropriate screening, and knowledge of risk factors for detection and progression of anal disease is critical to identify women at the highest risk for anal cancer. If this study is funded, we will also have the opportunity to compare these data to those obtained in studies of the cervix. Comparative studies at these anatomic sites should lead to significant advances in our understanding of site-specific risk factors in the pathogenesis of anogenital cancer both in HIV+ and HIV - women. Lastly, gender-specific factors may be studied, since we currently are conducting a very similar study of anal HPV infection and disease in HIV+ and HIV - men.